Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2

Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2 Sobha Sivaprasad, Sarega Gurudas, Inês Marques, Jean-François Girmens, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6247988/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Oct, 2025 Read the published version in Eye → Version 1 posted 9 You are reading this latest preprint version Abstract Background/Objectives: The aim of this study was to evaluate the change in visual acuity (VA) in participants with intermediate age-related macular degeneration (iAMD) over two years when categorized by the presence or absence of incomplete retinal and retinal pigment atrophy (iRORA) and subretinal drusenoid deposits (SDD). Subjects/Methods: In this multicentre cohort study, participants with iAMD were classified as: i) iAMD with no iRORA or SDD; ii) iAMD with SDD with no iRORA; iii) iAMD with iRORA with no SDD and iv) iAMD with iRORA and SDD. The change in VA over two years in the whole cohort and in each sub-category was analysed using a linear mixed effect model employing an unstructured covariance structure. Associations with age, sex and baseline VA were evaluated. Results 983 eyes from 805 participants were analysed. The mean baseline VA changed from 79.8 (SD 8.1) to 78 (SD 10.1) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at two years. All sub-categories showed a small decline in VA. The group with both iRORA and SDD experienced a statistically significant decline in VA from baseline across all time points (6,12, 18 and 24 months) and by month 24 a change of -2.72 ETDRS letters (95% CI -4.16, -1.28), P < 0.001 was observed. Increasing age and lower baseline visual acuity were associated with lower VA over two years. Conclusions Eyes with iAMD experience a small mean decline of approximately 2 letters over two years. Overall, these changes may not represent a clinically meaningful difference. Health sciences/Biomarkers Health sciences/Biomarkers/Predictive markers Figures Figure 1 Summary Box What was known before. Change in visual acuity (VA) from baseline is an established outcome measure for intervention trials in age-related macular degeneration. For regulatory approval, a preferred outcome is a prevention or improvement in VA of at least 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (a change of doubling of the visual angle). Eyes with intermediate AMD present with good visual acuity. Minimal changes in VA are expected in iAMD over time but the baseline determinants of VA loss are unclear. What this study adds. The average loss of VA in iAMD is only 2 ETDRS letters by two years and those with higher baseline VA and increasing age are more likely to lose VA, although the change is not clinically meaningful. Eyes with baseline visual acuity of 80 or more letters lost an average of -1.9 letters while those that presented with worse than 70 letters gained a mean of +2.39 letters. Therefore, it is advisable that clinical trials on iAMD stratify participants by baseline visual acuity. Only 13% of the study cohort lost 10 or more letters so preventing a 15-letter loss in this group by any intervention in eyes with iAMD require large sample size and longer follow-up than two years if the primary outcome is change in VA. Eyes with iAMD with incomplete retinal and retinal pigment epithelium atrophy or with geographic atrophy in the fellow eye are less likely to lose 5 or 10 or more letters by 2 years. Introduction Age-related macular degeneration (AMD) is a degenerative retinal disease that is predicted to affect 288 million elderly people worldwide by 2040. 1 The advanced forms are geographic atrophy (GA) and exudative neovascular AMD (nAMD). Despite available treatments for both these conditions, they are leading causes of severe central visual impairment in the elderly. 2 Prevention of progression to advanced AMD is key to preventing visual loss. And several clinical trials are on-going in this area. The presence of intermediate AMD (iAMD) is an established ocular risk factor for disease progression to advanced stages. Based on colour fundus photography of the macula, iAMD is characterised by at least one large druse (≥ 125um) and/or macular retinal pigment epithelial (RPE) disturbances associated with at least medium drusen. 3 However, most eyes with iAMD present with good visual acuity (VA) and decline in VA over time is slow. In order to design efficient clinical trials in iAMD, the change in VA over a short time frame in the control arm needs to be established, ideally in a natural history study. Despite the slow natural history of vision loss in iAMD, prevention of 3-line loss of VA or 15 Early Treatment Diabetic Retinopathy Study (ETDRS) loss is the acceptable regulatory endpoint for clinical trials on ocular therapies in this area. 4 Another important point is that a minimum clinical important difference (MCID) in VA is a change of at least 10 letters and for non-inferiority trials, an inferiority margin of about 5 letters is acceptable. 4 – 6 However, all these endpoints are challenging to achieve in clinical trials in iAMD because of good VA at baseline. A statistically significant difference between treatment and control arm in a superiority trial may be an option. An enriched study cohort with those at risk of VA loss in a short period of 1–2 years may be required. Several risk factors for fast progressors in eyes with iAMD have been identified on optical coherence tomography (OCT) but their associations with change in VA in a short period is unclear. These OCT features include drusen size, morphology, and volume; hyperreflective foci (HRF); subretinal drusenoid deposits (SDD), nascent GA, and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). 7 , 8 As these factors may co-exist, the presence of a combination of these changes may help identify a sub-group at risk of faster VA decline. Therefore, categorizing iAMD into various subgroups including more than one structural precursor of disease progression may improve our understanding on VA outcome in iAMD. As age of an individual and the disease state of the fellow eye are established risk factors for disease progression, these factors must also be considered in any risk models assessing VA loss in iAMD. INTERCEPT AMD is a collaborative network study conducted by European Vision Institute for Clinical Research (EVICR.net) Members in Europe that were willing to develop a multimodal image database of eyes with iAMD in at least one eye with at least three sets of available images over a two-year follow-up in a user-friendly EVICR.net Eye Platform. The aim of this study was to assess VA change in iAMD over two years by phenotyping iAMD into four categories using multimodal images. The associations of age, gender, baseline VA, fellow eye status, iAMD phenotype in study eye with VA change at 2 years were evaluated. Methods The study was managed by EVICR.net, Coimbra, Portugal that obtained the overarching institutional review board approval for the study. The EVICR.net also established data sharing agreements from sites to the EVICR.net Eye Platform and data and image transfer to Moorfields Eye Hospital via the EVICR.net Eye Platform. Each site then obtained their own regulatory approval required for each country. Informed consent from participants was obligatory only in some sites based on their regulatory approval while other countries considered this study as retrospective collection of routinely collected data and were exempt from further regulatory approval and informed consent. Selection of participants Each participant with iAMD was identified by site investigators from respective electronic medical records or imaging datasets. To be eligible for this study, at least one eye of the participant had to have a diagnosis of iAMD with records of at least 3 clinic visits with multimodal imaging across two years. Multimodal imaging included mandated Spectralis macular OCT scans with or without enhanced depth imaging and infrared imaging (IR). Fundus autofluorescence (FAF) was optional. Eyes with poor-quality images were excluded. Other exclusion criteria included eyes with bilateral exudative nAMD or geographic atrophy, any other co-existent ocular diseases including other types of macular atrophy or any individual who had opted out of their information being used for research nationally or locally at any Member Site. These criteria were screened by site personnel and reasons for exclusion as a study eye were recorded, where possible. Selection of study eye If only one eye had iAMD, the macula status of the non-study eye was graded on multimodal imaging as presence of cRORA; exudative nAMD, early AMD, healthy macula or ungradable due to poor image quality or have other macular pathology. If both eyes met the eligibility criteria of iAMD, they were both enrolled as study eyes. In order to subclassify iAMD, the Classification of Atrophy Meetings (CAM) group was used to define iRORA and cRORA on OCT. 9 SDD were identified in at least two imaging modalities. 10 Each eye with iAMD was further classified by the site personnel into the following pre-defined four categories at all three visits: Eyes with iAMD with no evidence of iRORA or SDD was considered as the eye with slowest rate of progression. The other three categories included iAMD with SDD with no iRORA; iAMD with iRORA with no SDD and iAMD with iRORA and SDD. In addition, age and AMD severity level of the fellow eye were collected as they are strong predictors of disease progression. Change in VA by disease state at two years The VA was recorded as ETDRS letter score at all sites. Methods of measurement of VA was recorded from the medical records from the index date and included VA with pinhole, VA with participant's glasses or best-corrected visual acuity (BCVA) if participants were refracted at the time of their VA assessment. The eye with better and worse VA was defined as the better seeing eye or worse seeing eye if a participant-level VA was considered. The VA change was analysed for the whole cohort as well as based on key demographic features, baseline study eye and fellow eye disease status. The change in VA over time in the better and worse seeing eye at baseline were analysed. Sample size A formal sample size estimation based on outcomes was not done as this study was aimed to collect a large research database for future studies. A sample size of 1000 eyes with VA records at baseline and over 2 years was considered a feasible resource for studying progression of different categories of iAMD and change in VA. Statistical analysis Summary statistics for VA across 2 years (baseline, months 6, 12, 18 and 24), stratified by baseline VA, age, sex, study eye diagnosis, and fellow eye diagnosis, were presented as mean (SD). Participant and eye-level characteristics for the total cohort of eyes were summarized using mean (SD) for normally distributed variables, median (IQR) for skewed variables and n (%) for categorical variables. The Linear mixed effects model (LMEM) for the continuous outcome VA score employing an unstructured covariance structure was used to account for the within-participant correlation between repeated measures over time and the nesting between eyes from the same participant. Differences in VA, 95% confidence intervals with p-values were summarised from the models. Mean change in VA from baseline, with 95% CIs and p-values were additionally summarised for all variables. Fixed effects adjusted for include the main effects of study eye diagnosis stage, fellow-eye diagnosis (exudative AMD or GA), age and sex and their interaction with time (defined as visits at baseline, 6, 12, 18 and 24 months) in separate linear mixed effects models. Baseline VA was not included as a covariate but instead were modelled as part of the outcome, consistent with growth curve modelling approaches. A LMEM assessing the association between baseline VA and VA across time (defined as visits at 6, 12, 18 and 24 months, i.e. which did not include baseline in the outcome) was also modelled to demonstrate the strength of baseline VA as a predictor for future VA. Models were accompanied with line plots that show the trajectory of VA across time, stratified by study eye diagnosis. The proportion of 5-letter and 10-letter losers were additionally analysed using unadjusted and age-gender adjusted logistic regression models via generalized estimating equations (GEE), with Odds Ratios (ORs), 95% CI and p-values were reported from the logistic regression models. For the analysis of eyes with unilateral eligibility (exudative AMD or GA in the fellow eye), within-participant correlations were based solely on repeated measures over time, as there is no nesting of data between the eyes. For the logistic regression models for exudative AMD or GA in the fellow eye, these were fitted using generalized linear models rather than generalized estimating equations. In sensitivity analysis, the natural history of BCVA, both overall and stratified by study eye diagnosis, was examined as the outcome instead of VA. This analysis was conducted on the subset of participants with available BCVA measurements. In a second sensitivity analysis, the natural history of VA, both overall and by study eye diagnosis, was evaluated after setting VA in study eyes that developed exudative AMD or GA during the study period to missing. This approach was used to assess the sensitivity of the results to potential declines in VA associated with these conditions. All statistical analyses were performed using R, with a significance level set at 5% for all tests. Complete case analysis was carried out. Data were visualized using the ggplot2 and sjPlot packages. Results A total of 819 participants were evaluated. Of these, 983 eyes of 805 participants met the eligibility criteria for iAMD, excluding 17 (1.7%) eyes classified as other macular atrophy less than 250 microns typically those due to vitelliform maculpathy (Table S1 ). The mean age was 75.8 years (SD 7.9 years), with 282 (35.0%) males. The mean baseline VA of the cohort was 79.8 (SD 8.1) [median VA 80.0 (IQR 75.0–85.0)] ETDRS letter score; with 630 (66.3%) eyes having VA 80 ETDRS letter score or better, while 3 (0.3%) had VA < 37 ETDRS letter score. Baseline VA was similar across the four categories of iAMD (Table 1 ). Table 1 Mean VA across time overall and by study eye diagnosis Variable Baseline M6 M12 M18 M24 N Mean (SD) N Mean (SD) N Mean (SD) N Mean (SD) N Mean (SD) Baseline BCVA, ETDRS letters <=69 70–79 80 or better - - 24 111 280 65.9 (9.3) 75.7 (5.8) 82.0 (4.7) 33 152 387 69.2 (12.1) 74.3 (7.4) 82.4 (5.6) 28 105 272 66.7 (12.6) 73.7 (9.3) 80.8 (6.4) 36 166 419 68.1 (12.4) 72.4 (10.6) 80.7 (8.1) Baseline VA, ETDRS letters <=69 70–79 80 or better - - 44 163 424 63.9 (11.3) 75.4 (6.6) 82.6 (4.6) 59 222 561 67.9 (12.1) 74.3 (8.1) 82.5 (5.4) 45 155 391 65.7 (12.8) 73.7 (9.7) 81.4 (6.2) 67 249 619 66.9 (12.7) 72.6 (10.6) 81.0 (7.6) iAMD diagnosis No iRORA & no SDD No iRORA & SDD iRORA & no SDD iRORA & SDD 315 367 110 158 80.3 (7.8) 79.5 (8.5) 80.5 (7.4) 78.9 (8.2) 211 278 85 100 80.0 (6.4) 79.5 (8.2) 80.0 (7) 77.1 (10) 295 352 99 144 79.8 (7.9) 79.4 (7.8) 80.2 (7.1) 76.9 (11) 190 273 75 98 78.3 (9.6) 78.7 (7.8) 80.0 (9.8) 75.5 (10.7) 321 385 114 163 78.2 (10.1) 77.3 (9.2) 79.2 (10.3) 76.3 (11.8) Exudative AMD in fellow eye Absent Present 124 490 79.6 (9.8) 78.8 (8.4) 74 377 80.2 (7.8) 79.1 (8.4) 114 467 79.7 (8.4) 78.0 (9.0) 63 357 77.2 (11.8) 77.8 (9.8) 128 499 77.2 (13.2) 76.8 (10.4) GA in fellow eye Absent Present 544 70 78.7 (8.8) 80.9 (7.2) 406 45 78.9 (8.5) 82.4 (4.4) 515 66 78.0 (9.1) 81.4 (5.8) 382 38 77.3 (10.4) 81.4 (5.5) 555 72 76.5 (11.3) 80.2 (7.9) Age, years < 75 75–84 85+ 417 427 106 82.0 (7.6) 78.6 (7.4) 75.1 (9.8) 284 307 83 81.5 (7.1) 78.6 (7.2) 75.1 (10.6) 388 401 101 81.3 (7.1) 78.2 (8.1) 75.1 (11.5) 269 291 76 80.7 (7.2) 76.8 (9.4) 74.5 (11.9) 434 437 112 80.0 (8.8) 76.1 (10.4) 74.3 (12.1) Sex Female Male 626 324 79.9 (7.7) 79.5 (8.8) 437 237 79.6 (7.8) 79.0 (8) 578 312 79.4 (8.7) 78.9 (7.8) 412 224 78.3 (9.3) 78.0 (9.1) 645 338 77.8 (10.3) 77.3 (9.8) Overall 950 79.8 (8.1) 674 79.4 (7.9) 890 79.2 (8.4) 636 78.2 (9.2) 983 77.7 (10.1) Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity. Change in VA across 2 years The mean VA at month 24 was 78 (SD 10.1) ETDRS letter score. Predicted VA in unadjusted linear mixed effects models (LMEM) show a decline in VA in the total cohort, and by study eye diagnosis across 2 years (Fig. 1 ). In adjusted LMEM’s the < 75-year age group and 75–84-year age group showed a change of -1.78 (95% CI -2.74, -0.82) ETDRS letters (P < .001) and − 2.92 (95% CI -3.85,-1.99) ETDRS letters (P < 0.001) respectively at 24 months (Table S2 ). A change of -2.23 ETDRS letters (95% CI -3.3, -1.16, P < 0.001) were observed in males and − 2.16 ETDRS letters (95% CI -2.94,-1.38, P < 0.001) in females at 24 months (Table 2 ). Table 2 VA based on disease state in study eye iAMD at baseline Baseline 2 years Change N Baseline VA, mean (SD) P-value* N VA at 2 years, mean (SD) P-value* N Change in VA at 2 years, mean (SD) P-value* VA in worse seeing eye in bilateral AMD (study eye) 178 81.3 (6.8) < 0.001 166 78.0 (8.8) < 0.001 166 -1.2 (7.1) .003 VA in better seeing eye in bilateral AMD (study eye) 83.5 (5.5) 80.6 (6.2) -2.8 (5.1) VA in iAMD study eye (with exudative AMD in non-study eye) 490 78.8 (8.4) .02 490 76.8 (10.4) .002 484 -2.1 (9.6) .23 VA in iAMD study eye (with GA in non-study eye) 70 80.9 (7.2) 70 80.2 (7.9) 68 -0.7 (8.8) Abbreviations: iAMD-intermediate age related macular degeneration; GA- geographic atrophy; VA-visual acuity. *paired t-test for VA comparing worse seeing and better seeing eye in bilateral AMD; unpaired t-test for unilateral iAMD From month 6 to month 24, eyes with baseline VA < = 69 ETDRS letters had a gain of 2.39 ETDRS letters (95% CI 0.28,4.49) (P = .026) while eyes with baseline VA 80 letters or better showed a change of -1.90 ETDRS letters (95% CI -2.64,-1.17) (P < .001). However, when considering only those who had BCVA measured at baseline, eyes in the < = 69 ETDRS letter group showed no change in VA over time (change = 1.4 [95% CI -1.53,4.33], P = .349). The iRORA and SDD group experienced a decline in VA from baseline across all time points and by month 24 a change of -2.72 ETDRS letters (95% CI -4.16, -1.28), P < 0.001 was observed. While eyes with no iRORA and no SDD and no iRORA but with SDD experienced a decrease in VA only at months 18 and 24 from baseline. Study eyes irrespective of fellow eyes having or not having exudative AMD showed a VA decline by month 24 in LMEM analysis: -1.96 ETDRS letters (95% CI -2.85,-1.07) in eyes with exudative AMD (P < .001) and − 2.66 (95% CI -4.43,-0.89) in eyes without exudative AMD (P = .003). However, eyes with GA in the fellow eye maintained better VA across all time points in the study eye, versus study eyes without GA in the fellow eye that showed decline in VA by month 24 (-2.24, SE 0.43, P < .001) and those with GA showing no change. VA based on better and worse seeing study eye Table 2 demonstrates the mean baseline VA and change in VA based on better or worse seeing eyes. By 2 years, in eyes with bilateral iAMD, the worse seeing eye changed by -2.8 ETDRS letters (SD 5.1) compared to -1.2 ETDRS letters (SD 7.1) in the better seeing eye (P = 0.003). At month 24, study eye VA was 76.8 (SD 10.4) in eyes with exudative AMD in the fellow eye compared to 80.2 (SD 7.9 in study eyes with GA in the fellow eye (P = .002). Study eyes with exudative AMD in the fellow eye changed by -2.1 ETDRS letters (SD 9.6) compared to -0.7 ETDRS letters (SD 8.8) in study eyes with GA in the non-study eye (P = .23). Associations for VA over time by baseline iAMD diagnosis, participant demographic variables and fellow eye status Increased age, lower baseline VA/BCVA and the absence of GA in the fellow eye were associated with reduced VA from baseline across all time points (Table 3 and S3). Study eyes with iRORA and SDD also had reduced VA across all time points relative to eyes with no iRORA and no SDD in unadjusted analysis only. Eyes with or without exudative AMD in the fellow-eye had no statistically significant difference in VA in the study eye across all time points. Table 3 Adjusted mean difference in VA over 2 years by study eye diagnosis, participant demographics and fellow eye status Baseline M6 M12 M18 M24 Characteristic Difference (95% CI) P-value Difference (95% CI) P-value Difference (95% CI) P-value Difference (95% CI) P-value Difference (95% CI) P-value Age Per 1 year increase -0.31(-0.38,-0.25) < 0.001 -0.31(-0.39,-0.24) < 0.001 -0.33(-0.4,-0.26) < 0.001 -0.34(-0.42,-0.26) < 0.001 -0.34(-0.42,-0.25) < 0.001 Age, years < 75 Ref Ref Ref Ref Ref 75–84 -2.78(-3.94,-1.63) < 0.001 -2.99(-4.18,-1.8) < 0.001 -3.21(-4.41,-2.01) < 0.001 -3.89(-5.26,-2.52) < 0.001 -4.01(-5.46,-2.55) < 0.001 85+ -6.5(-8.27,-4.73) < 0.001 -6.81(-8.63,-4.98) < 0.001 -7.03(-8.88,-5.18) < 0.001 -5.92(-8,-3.84) < 0.001 -5.82(-8.05,-3.59) < 0.001 Sex F Ref Ref Ref Ref Ref M -0.38(-1.51,0.76) 0.518 -0.51(-1.69,0.66) 0.39 -0.14(-1.33,1.04) 0.811 -0.04(-1.39,1.3) 0.95 -0.31(-1.75,1.12) 0.667 Baseline VA, ETDRS letters* 80 or better - - 70–79 - - -6.52(-7.51,-5.53) < 0.001 -7.08(-8.1,-6.06) < 0.001 -6.66(-7.85,-5.46) < 0.001 -7.34(-8.59,-6.08) < 0.001 <=69 - - -17.12(-18.8,-15.44) < 0.001 -13.02(-14.74,-11.29) < 0.001 -13.27(-15.23,-11.3) < 0.001 -12.81(-14.91,-10.71) < 0.001 Baseline BCVA, ETDRS letters* 80 or better - - 70–79 - - -6.22(-7.32,-5.12) < 0.001 -7.26(-8.44,-6.07) < 0.001 -6.92(-8.35,-5.49) < 0.001 -7.53(-9.08,-5.98) < 0.001 <=69 - - -14.34(-16.44,-12.25) < 0.001 -11.62(-13.87,-9.37) < 0.001 -11.32(-13.99,-8.65) < 0.001 -10.43(-13.39,-7.47) < 0.001 iAMD diagnosis No atrophy & no SDD Ref Ref Ref Ref Ref No atrophy & SDD -0.3(-1.54,0.94) 0.635 0.31(-0.97,1.6) 0.632 0.49(-0.81,1.78) 0.464 0.87(-0.61,2.34) 0.25 -0.2(-1.77,1.36) 0.801 iRORA & no SDD -0.12(-1.76,1.53) 0.889 -0.02(-1.73,1.69) 0.986 0.76(-1.01,2.53) 0.4 1.56(-0.42,3.54) 0.123 0.84(-1.25,2.93) 0.43 iRORA & SDD -0.76(-2.34,0.82) 0.345 -1.21(-2.88,0.45) 0.153 -1.44(-3.11,0.22) 0.089 -1.37(-3.25,0.52) 0.155 -1.34(-3.32,0.65) 0.187 Exudative AMD in fellow eye** Absent Present -0.39(-2.05,1.26) 0.642 0.00(-1.77,1.76) 0.997 -0.48(-2.23,1.28) 0.593 -0.51(-2.58,1.56) 0.631 0.04(-2.08,2.16) 0.971 GA in fellow eye** Absent Present 1.9(-0.18,3.99) 0.073 2.19(0,4.38) 0.050 2.85(0.66,5.04) 0.011 3.21(0.61,5.81) 0.015 3.35(0.69,6.01) 0.014 Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity. *For variables baseline VA and BCVA, the outcome was not defined to include baseline time. Eyes with missing baseline VA were not included, a total of N = 950 eyes from 782 participants were included for modelling. **For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time Change in VA: 5- and 10-letter loss across 2 years from baseline A total of 188/842 (22.8%) eyes had a 5 or more-letter loss at 1 year and 68/842 (8.1%) eyes lost 10 or more letters (Table S4 ). At 2 years, a total of 303/935 (32.4%) had a 5 or more-letter loss and 124/935 (13.3%) lost 10 or more letters (Table 4 ). Higher baseline VA had increased odds of 5-letter VA loss by 1 year (adjusted OR 1.03 per 1 letter increase, 95% CI 1.01–1.06, P = 0.004). Similarly, eyes with increased BCVA were at increased odds of 5 letter loss in VA by 1 year (adjusted OR 1.03, 95% CI 1.00-1.06, P = 0.024). By 2 years, eyes with iRORA and no SDD had reduced odds of 5-letter (adjusted OR 0.57, 95% CI 0.35–0.93, P = 0.024) and 10-letter VA loss (adjusted OR 0.42, 95% CI 0.18–0.96, P = 0.039) compared to eyes with no iRORA and no SDD (Table 4 ). At baseline, presence of GA in the fellow eye was associated with reduced odds of 5-letter VA loss by 1 year (OR 0.29, 95% CI 0.11–0.65, P = .005) and at 2 years (adjusted OR 0.38, 95% CI 0.19–0.71, P = 0.004) (Table 4 & S5). In addition, eyes with GA in the fellow eye had reduced odds of 10-letter loss in VA by 2 years (adjusted OR 0.26, 95% CI 0.06–0.72, P = 0.026). Unadjusted logistic regression analysis is presented in table S6 . Table 4 Proportion of 5 letter and 10 letters losers at 2 years using age and gender adjusted logistic regression models via generalized estimating equations Variable N =5 letters N = 303 Adjusted OR p-value =10 letters N = 124 Adjusted OR p-value Age_cat 935 < 75 290 (45.9%) 122 (40.3%) — 366 (45.1%) 46 (37.1%) — 75–84 270 (42.7%) 147 (48.5%) 1.31 (0.96–1.78) 0.086 349 (43.0%) 68 (54.8%) 1.57 (1.03–2.39) 0.037 85+ 72 (11.4%) 34 (11.2%) 1.17 (0.73–1.88) 0.51 96 (11.8%) 10 (8.1%) 0.86 (0.41–1.79) 0.68 Age, years 935 75.01(8.28) 75.96(7.42) 1.02 (1.00–1.03) 0.089 75.18(8.20) 76.27(6.66) 1.02 (1.00–1.04) 0.12 Sex 935 F 422 (66.8%) 194 (64.0%) — 541 (66.7%) 75 (60.5%) — M 210 (33.2%) 109 (36.0%) 1.09 (0.81–1.48) 0.55 270 (33.3%) 49 (39.5%) 1.29 (0.87–1.93) 0.21 Study eye diagnosis 935 No iRORA & no SDD 201 (31.8%) 108 (35.6%) — 264 (32.6%) 45 (36.3%) — No iRORA & SDD 236 (37.3%) 126 (41.6%) 0.97 (0.70–1.35) 0.85 311 (38.3%) 51 (41.1%) 0.97 (0.62–1.52) 0.89 iRORA & no SDD 84 (13.3%) 26 (8.6%) 0.57 (0.35–0.93) 0.024 103 (12.7%) 7 (5.6%) 0.42 (0.18–0.96) 0.039 iRORA & SDD 111 (17.6%) 43 (14.2%) 0.72 (0.46–1.11) 0.14 133 (16.4%) 21 (16.9%) 0.99 (0.56–1.74) 0.96 VA, ETDRS letters 935 80 or better 404 (63.9%) 215 (71.0%) — 543 (67.0%) 76 (61.3%) — 70–79 173 (27.4%) 76 (25.1%) 0.75 (0.53–1.05) 0.090 206 (25.4%) 43 (34.7%) 1.43 (0.93–2.20) 0.10 <=69 55 (8.7%) 12 (4.0%) 0.38 (0.20–0.74) 0.004 62 (7.6%) 5 (4.0%) 0.64 (0.26–1.57) 0.33 VA, ETDRS letters, V1 935 79(9) 81(7) 1.04 (1.02–1.06) < 0.001 80(8) 80(6) 1.00 (0.98–1.02) 0.96 BCVA, ETDRS letters, V1 621 80 or better 263 (64.3%) 156 (73.6%) — 366 (68.5%) 53 (60.9%) — 70–79 115 (28.1%) 51 (24.1%) 0.67 (0.45–1.00) 0.050 133 (24.9%) 33 (37.9%) 1.65 (0.99–2.75) 0.054 <=69 31 (7.6%) 5 (2.4%) 0.22 (0.08–0.61) 0.003 35 (6.6%) 1 (1.1%) 0.21 (0.03–1.34) 0.10 BCVA, ETDRS letters, V1 621 79(8) 81(7) 1.05 (1.02–1.09) < 0.001 80(8) 80(6) 1.00 (0.97–1.02) 0.88 Exudative in the fellow eye 603 0 84 (21.2%) 35 (17.0%) — 105 (20.3%) 14 (16.5%) — 1 313 (78.8%) 171 (83.0%) 1.28 (0.83–2.00) 0.28 413 (79.7%) 71 (83.5%) 1.25 (0.69–2.41) 0.47 GA in the fellow eye 603 0 341 (85.9%) 194 (94.2%) 453 (87.5%) 82 (96.5%) 1 56 (14.1%) 12 (5.8%) 0.38 (0.19–0.71) 0.004 65 (12.5%) 3 (3.5%) 0.26 (0.06–0.72) 0.026 Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy. ** glm logistic regression models fitted as only a single eye was included Sensitivity analysis In sensitivity analysis with BCVA as the outcome, there was negligible difference in predicted BCVA over time (Figure S1 ). At month 24, 53 (5.4%) eyes had progressed to GA and 79 (8.0%) eyes had exudative AMD. After excluding study eyes that developed exudative AMD or GA during the study, there was negligible difference in predicted VA over time (Figure S2 ). Additionally, eyes with missing VA over time were similar in distribution in baseline VA and study eye diagnoses to those with available data (Table S7 ). Discussion This study demonstrates that individuals with iAMD show minimal change in VA with an average loss of approximately 2 ETDRS letters over 2 years in the real-world irrespective of whether routinely collected VA or BCVA is used in the analysis. In the repeatability study within the MACUSTAR prospective cohort, the mean deviation of BCVA for each AMD group (early, intermediate and late AMD) was also within 2 ETDRS letters. 11 About 90% of individuals in our study presented with VA 70 letters or better and around 65% with at least 80 letters and so most individuals with iAMD have good vision creating a ceiling effect and therefore are more prone to lose rather than gain in VA. Only 13% had a 10 or more-letter loss by 2 years, an accepted criterion used to define a minimum clinically meaningful change in AMD and retinal vascular diseases. These results reinforce the fact that a prevention of 15 letter loss is not an achievable endpoint in iAMD if the control arm has a mean loss of only 2 letters over two years and very few eyes lost 10 or more letters. 4 These results also highlight the importance of baseline VA when evaluating and comparing clinical trials in iAMD. Those presenting with less than 70 letters, are also more likely to show an improvement in VA over the 2 years (mean + 2.39 ETDRS letters) compared to those presenting with VA of at least 80 letters (mean-1.9 ETDRS letters). It is well-established that lower VA present with greater variability and have a floor effect. Therefore, including patients with iAMD and VA less than 70 letters in clinical trials are more likely to result in surprising results especially if the intervention and control arms are not balanced for visual acuity. In addition, these findings may be interpreted as regression to the mean too. Another factor to consider is that increasing age at baseline was linked to lower VA across all time points (6,12, 18 and 24 months), with a decrease of -0.34 letters per year of baseline age at 24 months. Individuals aged 75–84 and those ≥ 85 years had lower VA outcome at all time points compared to < 69 age group irrespective of whether VA or BCVA was used for the analysis. Multiple age-related ocular changes including increasing thickness of the Bruch’s membrane, lipid accumulation, drusen volume and decreasing density of choriocapillaris may explain this observation. 12 , 13 The changes may also be confounded by non-AMD related VA decline with time. Interestingly, based on our classification of iAMD phenotypes, all groups showed a mean decline in VA over two years with no difference in mean change between them. After excluding study eyes that developed exudative AMD or GA during the study, there was negligible difference in predicted VA over time. Although eyes with SDD presented with lower VA and remained so at two years, the mean change did not reach statistical significance, in contrast to previous reports from smaller studies. 14 On the contrary, by 2 years, eyes with iRORA with no SDD had reduced odds of 5-letter (adjusted OR 0.57, 95% CI 0.35–0.93, P = 0.024) and 10-letter VA loss (adjusted OR 0.42, 95% CI 0.18–0.96, P = 0.039) compared to eyes with no iRORA and no SDD. These findings highlight that although iRORA is a risk factor for transition to cRORA, this structural precursor of atrophy is not associated with VA decline. Moreover, these findings may also be because iRORA may be reversible. 15 Our results also show that study eyes with GA in the fellow eye had reduced odds of both 5 and 10-letter loss in VA by 2 years. These observations demonstrate the slow course of the transition from iAMD to atrophy without substantial VA loss. In fact, the presence of GA in the fellow eye was associated with an improved VA outcome in the study eye across all time points, with a mean improvement of 3.35 letters at month 24 relative to study eyes without GA in the fellow eye. This finding raises the question whether participants with fellow eye GA attempts to read better at each visit than those without GA in the fellow eye. These within 1-line changes in VA in the natural course of iAMD has been confirmed in other studies and should also be considered when interpreting clinical trials in iAMD. 16 , 17 Although this is a large cohort with iAMD, the study has some limitations. The classification of eyes as presence or absence of SDD may be imperfect as the quantity or area of SDD may need to be incorporated for finer phenotyping. 18 Furthermore, the definition of iAMD assumes soft drusen are distributed in the macula and other risk characteristics of drusen such as hyporeflective drusen, cuticular drusen and drusenoid pigment epithelial detachment may also influence disease progression. 19 , 20 A more detailed grading of iAMD may elicit functional changes not revealed in this study. 17 Despite these limitations, the findings of this large cohort study provide insights for further research on VA change in iAMD especially for designing future clinical trials. Declarations Corresponding Author : Sobha Sivaprasad, National Institute of Health Research Moorfields Biomedical Research Centre and Clinical Research Facility, Moorfields Eye Hospital, 162, City Road, London, EC1V 2PD, UK. Email: [email protected] Funding/Support: The investigator-initiated study was funded by Boehringer Ingelheim International GmbH. Financial disclosures : Dr. Sivaprasad reported receiving financial support from AbbVie, Adverum, Amgen, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Pharmaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics and Sanofi. Sobha Sivaprasad is the Editor-in-Chief of EYE. Data availability statement: The data that support the findings of this study are all reported in this paper. Further details are available from the corresponding author and/or in the EVICR.net Eye Platform upon reasonable request. References Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-16. Deng Y, Qiao L, Du M, Qu C, Wan L, Li J, Huang L: Age-related macular degeneration: epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy. Genes Dis. 2022, 9:62–79. Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR; Beckman Initiative for Macular Research Classification Committee. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120(4):844–51. Csaky KG, Richman EA, Ferris FL 3rd: Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium. Invest Ophthalmol Vis Sci. 2008, 49:479 – 89. Beck RW, Maguire MG, Bressler NM, Glassman AR, Lindblad AS, Ferris FL. Visual acuity as an outcome measure in clinical trials of retinal diseases. Ophthalmology. 2007;114(10):1804–1809. Schmetterer L, Scholl H, Garhöfer G, Janeschitz-Kriegl L, Corvi F, Sadda SR, Medeiros FA: Endpoints for clinical trials in ophthalmology. Prog Retin Eye Res. 2023, 97:101160. Waldstein SM, Vogl WD, Bogunovic H, Sadeghipour A, Riedl S, Schmidt-Erfurth U. Characterization of Drusen and Hyperreflective Foci as Biomarkers for Disease Progression in Age-Related Macular Degeneration Using Artificial Intelligence in Optical Coherence Tomography. JAMA Ophthalmol. 2020;138(7):740–747. Lad EM, Finger RP, Guymer R. Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration. Ophthalmol Ther. 2023;12(6):2917–2941. Sadda SR, Guymer R, Holz FG, Schmitz-Valckenberg S, Curcio CA, Bird AC, Blodi BA, Bottoni F, Chakravarthy U, Chew EY, Csaky K, Danis RP, Fleckenstein M, Freund KB, Grunwald J, Hoyng CB, Jaffe GJ, Liakopoulos S, Monés JM, Pauleikhoff D, Rosenfeld PJ, Sarraf D, Spaide RF, Tadayoni R, Tufail A, Wolf S, Staurenghi G. Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3. Ophthalmology. 2018;125(4):537–548. doi: 10.1016/j.ophtha.2017.09.028. Epub 2017 Nov 2. Erratum in: Ophthalmology. 2019;126(1):177. Wu Z, Fletcher EL, Kumar H, Greferath U, Guymer RH. Reticular pseudodrusen: A critical phenotype in age-related macular degeneration. Prog Retin Eye Res. 2022;88:101017. Dunbar HMP, Behning C, Abdirahman A, Higgins BE, Binns AM, Terheyden JH, Zakaria N, Poor S, Finger RP, Leal S, Holz FG, Schmid M, Crabb DP, Rubin GS, Luhmann UFO; MACUSTAR Consortium. Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report. JAMA Ophthalmol. 2022;140(8):780–789. Pauleikhoff D, Harper CA, Marshall J, Bird AC.. Aging changes in Bruch's membrane: a histochemical and morphological study. Ophthalmology. 1990; 97: 171–178. Curcio CA, Kar D, Owsley C, Sloan KR, Ach T.. Age-related macular degeneration, a mathematically tractable disease. Invest Ophthalmol Vis Sci. 2024; 65: 4. Grewal MK, Chandra S, Gurudas S, Rasheed R, Sen P, Menon D, Bird A, Jeffery G, Sivaprasad S. Functional clinical endpoints and their correlations in eyes with AMD with and without subretinal drusenoid deposits-a pilot study. Eye (Lond). 2022;36(2):398–406. Santamaría J, Pagani F, Monés J. Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy? Eur J Ophthalmol. 2024 Oct 15:11206721241290263. Kaiser PK. Prospective evaluation of visual acuity assessment: a comparison of snellen versus ETDRS charts in clinical practice (An AOS Thesis). Trans Am Ophthalmol Soc. 2009;107:311 – 24. Leng T, Schwartz J, Nimke D, Gallivan M, Fevrier H, Rozario N, Schultz NM. Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. Ophthalmol Ther. 2023;12(1):325–340. Lad EM, Fang V, Tessier M, Rautanen A, Gayan J, Stinnett SS, Luhmann UFO. Longitudinal Evaluation of Visual Function Impairments in Early and Intermediate Age-Related Macular Degeneration Participants. Ophthalmol Sci. 2022;2(3):100173. Schneck ME, Lott LA, Haegerstrom-Portnoy G, Hewlett S, Gauer BM, Zaidi A. Visual Function in Eyes with Intermediate AMD with and without Retinal Pigment Abnormalities. Optom Vis Sci. 2021;98(1):64–72. Davis MD, Gangnon RE, Lee LY, Hubbard LD, Klein BEK, Klein R, Ferris FL, Bressler SB, Milton RC, Group AREDS The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005;123(11):1484–1498. Additional Declarations There is conflict of interest Supplementary Files FigureS1intercept2.docx Figure S1. Sensitivity analysis on BCVA as the outcome Abbreviations: Abbreviations: iAMD-intermediate age-related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity. FigureS2intercept2.docx Figure S2. Sensitivity analysis after setting to missing eyes that converted to wet AMD or GA during the study period Abbreviations: Abbreviations: iAMD-intermediate age-related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy. TableS1intercept2.docx Table S1. Baseline summary statistics by study eye diagnosis Abbreviations: iAMD-intermediate age-related macular degeneration; cRORA- complete retinal and retinal pigment epithelial atrophy; iRORA- incomplete retinal and retinal pigment epithelial atrophy; MNV-macular neovascularisation; SDD-subretinal drusenoid deposits; VA-visual acuity; ETDRS-Early treatment Diabetic Retinopathy Study; GA-geographic atrophy. TableS2intercept2.docx Table S2. Change in VA over time from baseline by iAMD diagnosis, participant demographic variables and fellow eye status Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity. *Change in VA from M6 not baseline for baseline VA and BCVA variables. Eyes with missing baseline VA were not included, a total of N=950 eyes from 782 participants were included for modelling. **For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time TableS3intercept2.docx Table S3. Unadjusted mean difference in VA over 2 years by study eye diagnosis, participant demographics and fellow eye status Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy. *For variables baseline VA and BCVA, the outcome was not defined to include baseline time. Eyes with missing baseline VA were not included, a total of N=950 eyes from 782 participants were included for modelling. **For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time TableS4intercept2.docx Table S4. Proportion of 5-letter losers and 10-letter losers by 1 year Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy. ** For exudative and GA variables glm logistic regression models fitted as only one eye per participant was included TableS5intercept2.docx Table S5. Unadjusted and age-gender adjusted logistic regression models via generalized estimating equations (GEE) for 5-letter and 10-letter loss at 1 year Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy. ** For exudative and GA variables glm logistic regression models fitted as only one eye per participant was included TableS6intercept2.docx Table S6. Unadjusted logistic regression models via generalized estimating equations for 5-letter and 10-letter losers at 2 years Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy. ** glm logistic regression models fitted as only a single eye was included TableS7intercept2.docx Table S7. Missing data characteristics Abbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; VA-visual acuity. TableS8intercept2.docx Table S8; Intercept-AMD Study Group Cite Share Download PDF Status: Published Journal Publication published 17 Oct, 2025 Read the published version in Eye → Version 1 posted Editorial decision: revise 10 Jun, 2025 Review # 2 received at journal 04 Jun, 2025 Reviewer # 2 agreed at journal 15 May, 2025 Review # 1 received at journal 10 May, 2025 Reviewer # 1 agreed at journal 21 Apr, 2025 Reviewers invited by journal 01 Apr, 2025 Editor assigned by journal 27 Mar, 2025 Submission checks completed at journal 19 Mar, 2025 First submitted to journal 17 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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23:25:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6247988/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6247988/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-025-04062-z","type":"published","date":"2025-10-17T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81700124,"identity":"60587392-cf49-45bb-85a3-be9669e53dc9","added_by":"auto","created_at":"2025-04-30 13:04:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":99696,"visible":true,"origin":"","legend":"\u003cp\u003eNatural history of VA overall and by iAMD diagnosis\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; VA-visual acuity; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/3cdd14364117f3f3e6f57c08.png"},{"id":93827672,"identity":"3d6c70ed-d9a3-46b8-99be-d76553d9a090","added_by":"auto","created_at":"2025-10-18 07:09:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1622106,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/f0cdb732-039c-4b75-8fc8-e6c48ee7510f.pdf"},{"id":81699962,"identity":"e6c4b3fc-8300-4f4f-92ef-d786bb382988","added_by":"auto","created_at":"2025-04-30 13:04:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":223846,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eFigure S1. Sensitivity analysis on BCVA as the outcome\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: Abbreviations: iAMD-intermediate age-related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity.\u003c/p\u003e","description":"","filename":"FigureS1intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/5ffc461f95304e8d37a1520b.docx"},{"id":81699977,"identity":"ab50cb91-2bd4-436f-a048-1396ba82764e","added_by":"auto","created_at":"2025-04-30 13:04:12","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":238725,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eFigure S2. Sensitivity analysis after setting to missing eyes that converted to wet AMD or GA during the study period\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: Abbreviations: iAMD-intermediate age-related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy.\u003c/p\u003e","description":"","filename":"FigureS2intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/69a2248224c5103e92754e29.docx"},{"id":81699733,"identity":"cf34c0ab-a0cc-4feb-a507-3cf7407305ff","added_by":"auto","created_at":"2025-04-30 13:03:54","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":20840,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S1. Baseline summary statistics by study eye diagnosis\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age-related macular degeneration; cRORA- complete retinal and retinal pigment epithelial atrophy; iRORA- incomplete retinal and retinal pigment epithelial atrophy; MNV-macular neovascularisation; SDD-subretinal drusenoid deposits; VA-visual acuity; ETDRS-Early treatment Diabetic Retinopathy Study; GA-geographic atrophy.\u003c/p\u003e","description":"","filename":"TableS1intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/ae2c3aee037d9a456ceb5a19.docx"},{"id":81699971,"identity":"ec55a6ac-9e3c-41d9-b3eb-13f2518efc77","added_by":"auto","created_at":"2025-04-30 13:04:11","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":20999,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S2. Change in VA over time from baseline by iAMD diagnosis, participant demographic variables and fellow eye status\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity. *Change in VA from M6 not baseline for baseline VA and BCVA variables. Eyes with missing baseline VA were not included, a total of N=950 eyes from 782 participants were included for modelling. **For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time\u003c/p\u003e","description":"","filename":"TableS2intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/63a8752dee9835a51aeb835e.docx"},{"id":81699982,"identity":"bbb41e04-05a0-448d-8bdf-5ee521a049af","added_by":"auto","created_at":"2025-04-30 13:04:14","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":21774,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S3. Unadjusted mean difference in VA over 2 years by study eye diagnosis, participant demographics and fellow eye status\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy.\u003c/p\u003e\n\u003cp\u003e*For variables baseline VA and BCVA, the outcome was not defined to include baseline time. Eyes with missing baseline VA were not included, a total of N=950 eyes from 782 participants were included for modelling.\u003c/p\u003e\n\u003cp\u003e**For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time\u003c/p\u003e","description":"","filename":"TableS3intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/020283e9a292ac9f6f6fd798.docx"},{"id":81699614,"identity":"19f2b336-5fee-4e9b-8dfa-7d82ebf47478","added_by":"auto","created_at":"2025-04-30 13:03:47","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":18922,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S4. Proportion of 5-letter losers and 10-letter losers by 1 year\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy.\u003c/p\u003e\n\u003cp\u003e** For exudative and GA variables glm logistic regression models fitted as only one eye per participant was included\u003c/p\u003e","description":"","filename":"TableS4intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/33671fa8feba9699d4466b5c.docx"},{"id":81699984,"identity":"36c725df-2745-441c-a9a5-08152ec1a45d","added_by":"auto","created_at":"2025-04-30 13:04:15","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":21578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S5. Unadjusted and age-gender adjusted logistic regression models via generalized estimating equations (GEE) for 5-letter and 10-letter loss at 1 year\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity; GA-geographic atrophy.\u003c/p\u003e\n\u003cp\u003e** For exudative and GA variables glm logistic regression models fitted as only one eye per participant was included\u003c/p\u003e","description":"","filename":"TableS5intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/b62a9a0f1dbecbf8a6e59f6f.docx"},{"id":81699856,"identity":"5ee43b65-61ba-4a28-8303-b5860666e7eb","added_by":"auto","created_at":"2025-04-30 13:03:58","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":18920,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S6. Unadjusted logistic regression models via generalized estimating equations for 5-letter and 10-letter losers at 2 years\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy. ** glm logistic regression models fitted as only a single eye was included\u003c/p\u003e","description":"","filename":"TableS6intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/06d5849714473ed60248c16d.docx"},{"id":81699898,"identity":"67e0b258-dd6f-4ee0-8a41-96ffe04502a9","added_by":"auto","created_at":"2025-04-30 13:04:01","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":16813,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S7. Missing data characteristics\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; ETDRS-Early treatment Diabetic Retinopathy Study; VA-visual acuity.\u003c/p\u003e","description":"","filename":"TableS7intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/9140d1885951b19721483d11.docx"},{"id":81699905,"identity":"69851682-de6f-416f-a679-f3272ed3041d","added_by":"auto","created_at":"2025-04-30 13:04:02","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":17313,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eTable S8; \u003c/u\u003e\u003cu\u003e\u003cstrong\u003eIntercept-AMD Study Group\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e","description":"","filename":"TableS8intercept2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6247988/v1/098b5ef93776e6259dd8ce48.docx"}],"financialInterests":"There is conflict of interest","formattedTitle":"Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2","fulltext":[{"header":"Summary Box","content":"\u003cp\u003eWhat was known before.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eChange in visual acuity (VA) from baseline is an established outcome measure for intervention trials in age-related macular degeneration.\u003c/li\u003e\n \u003cli\u003eFor regulatory approval, a preferred outcome is a prevention or improvement in VA of at least 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (a change of doubling of the visual angle). \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEyes with intermediate AMD present with good visual acuity.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMinimal changes in VA are expected in iAMD over time but the baseline determinants of VA loss are unclear.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWhat this study adds.\u0026nbsp;\u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n \u003cli\u003eThe average loss of VA in iAMD is only 2 ETDRS letters by two years and those with higher baseline VA and increasing age are more likely to lose VA, although the change is not clinically meaningful.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEyes with baseline visual acuity of 80 or more letters lost an average of -1.9 letters while those that presented with worse than 70 letters gained a mean of +2.39 letters. Therefore, it is advisable that clinical trials on iAMD stratify participants by baseline visual acuity. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOnly 13% of the study cohort lost 10 or more letters so preventing a 15-letter loss in this group by any intervention in eyes with iAMD require large sample size and longer follow-up than two years if the primary outcome is change in VA.\u003c/li\u003e\n \u003cli\u003eEyes with iAMD with incomplete retinal and retinal pigment epithelium atrophy or with geographic atrophy in the fellow eye are less likely to lose 5 or 10 or more letters by 2 years.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eAge-related macular degeneration (AMD) is a degenerative retinal disease that is predicted to affect 288\u0026nbsp;million elderly people worldwide by 2040.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The advanced forms are geographic atrophy (GA) and exudative neovascular AMD (nAMD). Despite available treatments for both these conditions, they are leading causes of severe central visual impairment in the elderly.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Prevention of progression to advanced AMD is key to preventing visual loss. And several clinical trials are on-going in this area.\u003c/p\u003e \u003cp\u003eThe presence of intermediate AMD (iAMD) is an established ocular risk factor for disease progression to advanced stages. Based on colour fundus photography of the macula, iAMD is characterised by at least one large druse (\u0026ge;\u0026thinsp;125um) and/or macular retinal pigment epithelial (RPE) disturbances associated with at least medium drusen.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e However, most eyes with iAMD present with good visual acuity (VA) and decline in VA over time is slow. In order to design efficient clinical trials in iAMD, the change in VA over a short time frame in the control arm needs to be established, ideally in a natural history study.\u003c/p\u003e \u003cp\u003eDespite the slow natural history of vision loss in iAMD, prevention of 3-line loss of VA or 15 Early Treatment Diabetic Retinopathy Study (ETDRS) loss is the acceptable regulatory endpoint for clinical trials on ocular therapies in this area.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Another important point is that a minimum clinical important difference (MCID) in VA is a change of at least 10 letters and for non-inferiority trials, an inferiority margin of about 5 letters is acceptable.\u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, all these endpoints are challenging to achieve in clinical trials in iAMD because of good VA at baseline. A statistically significant difference between treatment and control arm in a superiority trial may be an option. An enriched study cohort with those at risk of VA loss in a short period of 1\u0026ndash;2 years may be required.\u003c/p\u003e \u003cp\u003eSeveral risk factors for fast progressors in eyes with iAMD have been identified on optical coherence tomography (OCT) but their associations with change in VA in a short period is unclear. These OCT features include drusen size, morphology, and volume; hyperreflective foci (HRF); subretinal drusenoid deposits (SDD), nascent GA, and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA).\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e As these factors may co-exist, the presence of a combination of these changes may help identify a sub-group at risk of faster VA decline. Therefore, categorizing iAMD into various subgroups including more than one structural precursor of disease progression may improve our understanding on VA outcome in iAMD. As age of an individual and the disease state of the fellow eye are established risk factors for disease progression, these factors must also be considered in any risk models assessing VA loss in iAMD.\u003c/p\u003e \u003cp\u003eINTERCEPT AMD is a collaborative network study conducted by European Vision Institute for Clinical Research (EVICR.net) Members in Europe that were willing to develop a multimodal image database of eyes with iAMD in at least one eye with at least three sets of available images over a two-year follow-up in a user-friendly EVICR.net Eye Platform. The aim of this study was to assess VA change in iAMD over two years by phenotyping iAMD into four categories using multimodal images. The associations of age, gender, baseline VA, fellow eye status, iAMD phenotype in study eye with VA change at 2 years were evaluated.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The study was managed by EVICR.net, Coimbra, Portugal that obtained the overarching institutional review board approval for the study. The EVICR.net also established data sharing agreements from sites to the EVICR.net Eye Platform and data and image transfer to Moorfields Eye Hospital via the EVICR.net Eye Platform. Each site then obtained their own regulatory approval required for each country. Informed consent from participants was obligatory only in some sites based on their regulatory approval while other countries considered this study as retrospective collection of routinely collected data and were exempt from further regulatory approval and informed consent.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSelection of participants\u003c/h2\u003e \u003cp\u003eEach participant with iAMD was identified by site investigators from respective electronic medical records or imaging datasets. To be eligible for this study, at least one eye of the participant had to have a diagnosis of iAMD with records of at least 3 clinic visits with multimodal imaging across two years. Multimodal imaging included mandated Spectralis macular OCT scans with or without enhanced depth imaging and infrared imaging (IR). Fundus autofluorescence (FAF) was optional. Eyes with poor-quality images were excluded. Other exclusion criteria included eyes with bilateral exudative nAMD or geographic atrophy, any other co-existent ocular diseases including other types of macular atrophy or any individual who had opted out of their information being used for research nationally or locally at any Member Site. These criteria were screened by site personnel and reasons for exclusion as a study eye were recorded, where possible.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSelection of study eye\u003c/h3\u003e\n\u003cp\u003eIf only one eye had iAMD, the macula status of the non-study eye was graded on multimodal imaging as presence of cRORA; exudative nAMD, early AMD, healthy macula or ungradable due to poor image quality or have other macular pathology. If both eyes met the eligibility criteria of iAMD, they were both enrolled as study eyes.\u003c/p\u003e \u003cp\u003eIn order to subclassify iAMD, the Classification of Atrophy Meetings (CAM) group was used to define iRORA and cRORA on OCT.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e SDD were identified in at least two imaging modalities.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Each eye with iAMD was further classified by the site personnel into the following pre-defined four categories at all three visits: Eyes with iAMD with no evidence of iRORA or SDD was considered as the eye with slowest rate of progression. The other three categories included iAMD with SDD with no iRORA; iAMD with iRORA with no SDD and iAMD with iRORA and SDD. In addition, age and AMD severity level of the fellow eye were collected as they are strong predictors of disease progression.\u003c/p\u003e\n\u003ch3\u003eChange in VA by disease state at two years\u003c/h3\u003e\n\u003cp\u003eThe VA was recorded as ETDRS letter score at all sites. Methods of measurement of VA was recorded from the medical records from the index date and included VA with pinhole, VA with participant's glasses or best-corrected visual acuity (BCVA) if participants were refracted at the time of their VA assessment. The eye with better and worse VA was defined as the better seeing eye or worse seeing eye if a participant-level VA was considered. The VA change was analysed for the whole cohort as well as based on key demographic features, baseline study eye and fellow eye disease status. The change in VA over time in the better and worse seeing eye at baseline were analysed.\u003c/p\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eA formal sample size estimation based on outcomes was not done as this study was aimed to collect a large research database for future studies. A sample size of 1000 eyes with VA records at baseline and over 2 years was considered a feasible resource for studying progression of different categories of iAMD and change in VA.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSummary statistics for VA across 2 years (baseline, months 6, 12, 18 and 24), stratified by baseline VA, age, sex, study eye diagnosis, and fellow eye diagnosis, were presented as mean (SD). Participant and eye-level characteristics for the total cohort of eyes were summarized using mean (SD) for normally distributed variables, median (IQR) for skewed variables and n (%) for categorical variables.\u003c/p\u003e \u003cp\u003eThe Linear mixed effects model (LMEM) for the continuous outcome VA score employing an unstructured covariance structure was used to account for the within-participant correlation between repeated measures over time and the nesting between eyes from the same participant. Differences in VA, 95% confidence intervals with p-values were summarised from the models. Mean change in VA from baseline, with 95% CIs and p-values were additionally summarised for all variables.\u003c/p\u003e \u003cp\u003eFixed effects adjusted for include the main effects of study eye diagnosis stage, fellow-eye diagnosis (exudative AMD or GA), age and sex and their interaction with time (defined as visits at baseline, 6, 12, 18 and 24 months) in separate linear mixed effects models. Baseline VA was not included as a covariate but instead were modelled as part of the outcome, consistent with growth curve modelling approaches. A LMEM assessing the association between baseline VA and VA across time (defined as visits at 6, 12, 18 and 24 months, i.e. which did not include baseline in the outcome) was also modelled to demonstrate the strength of baseline VA as a predictor for future VA. Models were accompanied with line plots that show the trajectory of VA across time, stratified by study eye diagnosis. The proportion of 5-letter and 10-letter losers were additionally analysed using unadjusted and age-gender adjusted logistic regression models via generalized estimating equations (GEE), with Odds Ratios (ORs), 95% CI and p-values were reported from the logistic regression models.\u003c/p\u003e \u003cp\u003eFor the analysis of eyes with unilateral eligibility (exudative AMD or GA in the fellow eye), within-participant correlations were based solely on repeated measures over time, as there is no nesting of data between the eyes. For the logistic regression models for exudative AMD or GA in the fellow eye, these were fitted using generalized linear models rather than generalized estimating equations.\u003c/p\u003e \u003cp\u003eIn sensitivity analysis, the natural history of BCVA, both overall and stratified by study eye diagnosis, was examined as the outcome instead of VA. This analysis was conducted on the subset of participants with available BCVA measurements. In a second sensitivity analysis, the natural history of VA, both overall and by study eye diagnosis, was evaluated after setting VA in study eyes that developed exudative AMD or GA during the study period to missing. This approach was used to assess the sensitivity of the results to potential declines in VA associated with these conditions.\u003c/p\u003e \u003cp\u003eAll statistical analyses were performed using R, with a significance level set at 5% for all tests. Complete case analysis was carried out. Data were visualized using the ggplot2 and sjPlot packages.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 819 participants were evaluated. Of these, 983 eyes of 805 participants met the eligibility criteria for iAMD, excluding 17 (1.7%) eyes classified as other macular atrophy less than 250 microns typically those due to vitelliform maculpathy (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The mean age was 75.8 years (SD 7.9 years), with 282 (35.0%) males. The mean baseline VA of the cohort was 79.8 (SD 8.1) [median VA 80.0 (IQR 75.0\u0026ndash;85.0)] ETDRS letter score; with 630 (66.3%) eyes having VA 80 ETDRS letter score or better, while 3 (0.3%) had VA\u0026thinsp;\u0026lt;\u0026thinsp;37 ETDRS letter score. Baseline VA was similar across the four categories of iAMD (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean VA across time overall and by study eye diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eM6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eM12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eM18\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eM24\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline BCVA, ETDRS letters\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e111\u003c/p\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.9 (9.3)\u003c/p\u003e \u003cp\u003e75.7 (5.8)\u003c/p\u003e \u003cp\u003e82.0 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33\u003c/p\u003e \u003cp\u003e152\u003c/p\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e69.2 (12.1)\u003c/p\u003e \u003cp\u003e74.3 (7.4)\u003c/p\u003e \u003cp\u003e82.4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e105\u003c/p\u003e \u003cp\u003e272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e66.7 (12.6)\u003c/p\u003e \u003cp\u003e73.7 (9.3)\u003c/p\u003e \u003cp\u003e80.8 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e36\u003c/p\u003e \u003cp\u003e166\u003c/p\u003e \u003cp\u003e419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e68.1 (12.4)\u003c/p\u003e \u003cp\u003e72.4 (10.6)\u003c/p\u003e \u003cp\u003e80.7 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline VA, ETDRS letters\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003cp\u003e163\u003c/p\u003e \u003cp\u003e424\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63.9 (11.3)\u003c/p\u003e \u003cp\u003e75.4 (6.6)\u003c/p\u003e \u003cp\u003e82.6 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59\u003c/p\u003e \u003cp\u003e222\u003c/p\u003e \u003cp\u003e561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e67.9 (12.1)\u003c/p\u003e \u003cp\u003e74.3 (8.1)\u003c/p\u003e \u003cp\u003e82.5 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e45\u003c/p\u003e \u003cp\u003e155\u003c/p\u003e \u003cp\u003e391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e65.7 (12.8)\u003c/p\u003e \u003cp\u003e73.7 (9.7)\u003c/p\u003e \u003cp\u003e81.4 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e67\u003c/p\u003e \u003cp\u003e249\u003c/p\u003e \u003cp\u003e619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e66.9 (12.7)\u003c/p\u003e \u003cp\u003e72.6 (10.6)\u003c/p\u003e \u003cp\u003e81.0 (7.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eiAMD diagnosis\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNo iRORA \u0026amp; no SDD\u003c/p\u003e \u003cp\u003eNo iRORA \u0026amp; SDD\u003c/p\u003e \u003cp\u003eiRORA \u0026amp; no SDD\u003c/p\u003e \u003cp\u003eiRORA \u0026amp; SDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e315\u003c/p\u003e \u003cp\u003e367\u003c/p\u003e \u003cp\u003e110\u003c/p\u003e \u003cp\u003e158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.3 (7.8)\u003c/p\u003e \u003cp\u003e79.5 (8.5)\u003c/p\u003e \u003cp\u003e80.5 (7.4)\u003c/p\u003e \u003cp\u003e78.9 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e211\u003c/p\u003e \u003cp\u003e278\u003c/p\u003e \u003cp\u003e85\u003c/p\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.0 (6.4)\u003c/p\u003e \u003cp\u003e79.5 (8.2)\u003c/p\u003e \u003cp\u003e80.0 (7)\u003c/p\u003e \u003cp\u003e77.1 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e295\u003c/p\u003e \u003cp\u003e352\u003c/p\u003e \u003cp\u003e99\u003c/p\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e79.8 (7.9)\u003c/p\u003e \u003cp\u003e79.4 (7.8)\u003c/p\u003e \u003cp\u003e80.2 (7.1)\u003c/p\u003e \u003cp\u003e76.9 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e190\u003c/p\u003e \u003cp\u003e273\u003c/p\u003e \u003cp\u003e75\u003c/p\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e78.3 (9.6)\u003c/p\u003e \u003cp\u003e78.7 (7.8)\u003c/p\u003e \u003cp\u003e80.0 (9.8)\u003c/p\u003e \u003cp\u003e75.5 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e321\u003c/p\u003e \u003cp\u003e385\u003c/p\u003e \u003cp\u003e114\u003c/p\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e78.2 (10.1)\u003c/p\u003e \u003cp\u003e77.3 (9.2)\u003c/p\u003e \u003cp\u003e79.2 (10.3)\u003c/p\u003e \u003cp\u003e76.3 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExudative AMD in fellow eye\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124\u003c/p\u003e \u003cp\u003e490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79.6 (9.8)\u003c/p\u003e \u003cp\u003e78.8 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74\u003c/p\u003e \u003cp\u003e377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.2 (7.8)\u003c/p\u003e \u003cp\u003e79.1 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e114\u003c/p\u003e \u003cp\u003e467\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e79.7 (8.4)\u003c/p\u003e \u003cp\u003e78.0 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63\u003c/p\u003e \u003cp\u003e357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e77.2 (11.8)\u003c/p\u003e \u003cp\u003e77.8 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e128\u003c/p\u003e \u003cp\u003e499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e77.2 (13.2)\u003c/p\u003e \u003cp\u003e76.8 (10.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGA in fellow eye\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e544\u003c/p\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.7 (8.8)\u003c/p\u003e \u003cp\u003e80.9 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e406\u003c/p\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.9 (8.5)\u003c/p\u003e \u003cp\u003e82.4 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e515\u003c/p\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78.0 (9.1)\u003c/p\u003e \u003cp\u003e81.4 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e382\u003c/p\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e77.3 (10.4)\u003c/p\u003e \u003cp\u003e81.4 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e555\u003c/p\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e76.5 (11.3)\u003c/p\u003e \u003cp\u003e80.2 (7.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;75\u003c/p\u003e \u003cp\u003e75\u0026ndash;84\u003c/p\u003e \u003cp\u003e85+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e417\u003c/p\u003e \u003cp\u003e427\u003c/p\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.0 (7.6)\u003c/p\u003e \u003cp\u003e78.6 (7.4)\u003c/p\u003e \u003cp\u003e75.1 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e284\u003c/p\u003e \u003cp\u003e307\u003c/p\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81.5 (7.1)\u003c/p\u003e \u003cp\u003e78.6 (7.2)\u003c/p\u003e \u003cp\u003e75.1 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e388\u003c/p\u003e \u003cp\u003e401\u003c/p\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e81.3 (7.1)\u003c/p\u003e \u003cp\u003e78.2 (8.1)\u003c/p\u003e \u003cp\u003e75.1 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003cp\u003e291\u003c/p\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e80.7 (7.2)\u003c/p\u003e \u003cp\u003e76.8 (9.4)\u003c/p\u003e \u003cp\u003e74.5 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e434\u003c/p\u003e \u003cp\u003e437\u003c/p\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e80.0 (8.8)\u003c/p\u003e \u003cp\u003e76.1 (10.4)\u003c/p\u003e \u003cp\u003e74.3 (12.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e626\u003c/p\u003e \u003cp\u003e324\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79.9 (7.7)\u003c/p\u003e \u003cp\u003e79.5 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e437\u003c/p\u003e \u003cp\u003e237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79.6 (7.8)\u003c/p\u003e \u003cp\u003e79.0 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e578\u003c/p\u003e \u003cp\u003e312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e79.4 (8.7)\u003c/p\u003e \u003cp\u003e78.9 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e412\u003c/p\u003e \u003cp\u003e224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e78.3 (9.3)\u003c/p\u003e \u003cp\u003e78.0 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e645\u003c/p\u003e \u003cp\u003e338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e77.8 (10.3)\u003c/p\u003e \u003cp\u003e77.3 (9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79.8 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e674\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79.4 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e79.2 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e78.2 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e983\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e77.7 (10.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eChange in VA across 2 years\u003c/h3\u003e\n\u003cp\u003eThe mean VA at month 24 was 78 (SD 10.1) ETDRS letter score. Predicted VA in unadjusted linear mixed effects models (LMEM) show a decline in VA in the total cohort, and by study eye diagnosis across 2 years (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn adjusted LMEM\u0026rsquo;s the \u0026lt;\u0026thinsp;75-year age group and 75\u0026ndash;84-year age group showed a change of -1.78 (95% CI -2.74, -0.82) ETDRS letters (P\u0026thinsp;\u0026lt;\u0026thinsp;.001) and \u0026minus;\u0026thinsp;2.92 (95% CI -3.85,-1.99) ETDRS letters (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) respectively at 24 months (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). A change of -2.23 ETDRS letters (95% CI -3.3, -1.16, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were observed in males and \u0026minus;\u0026thinsp;2.16 ETDRS letters (95% CI -2.94,-1.38, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in females at 24 months (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVA based on disease state in study eye iAMD at baseline\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e2 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline VA, mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVA at 2 years, mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-value*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eChange in VA at 2 years, mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eP-value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVA in worse seeing eye in bilateral AMD (study eye)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81.3 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e78.0 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-1.2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVA in better seeing eye in bilateral AMD (study eye)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e83.5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e80.6 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-2.8 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVA in iAMD study eye (with exudative AMD in non-study eye)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78.8 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e76.8 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e484\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-2.1 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVA in iAMD study eye (with GA in non-study eye)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80.9 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e80.2 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-0.7 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eAbbreviations: iAMD-intermediate age related macular degeneration; GA- geographic atrophy; VA-visual acuity. *paired t-test for VA comparing worse seeing and better seeing eye in bilateral AMD; unpaired t-test for unilateral iAMD\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFrom month 6 to month 24, eyes with baseline VA\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;69 ETDRS letters had a gain of 2.39 ETDRS letters (95% CI 0.28,4.49) (P\u0026thinsp;=\u0026thinsp;.026) while eyes with baseline VA 80 letters or better showed a change of -1.90 ETDRS letters (95% CI -2.64,-1.17) (P\u0026thinsp;\u0026lt;\u0026thinsp;.001). However, when considering only those who had BCVA measured at baseline, eyes in the \u0026lt;\u0026thinsp;=\u0026thinsp;69 ETDRS letter group showed no change in VA over time (change\u0026thinsp;=\u0026thinsp;1.4 [95% CI -1.53,4.33], P\u0026thinsp;=\u0026thinsp;.349).\u003c/p\u003e \u003cp\u003eThe iRORA and SDD group experienced a decline in VA from baseline across all time points and by month 24 a change of -2.72 ETDRS letters (95% CI -4.16, -1.28), P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 was observed. While eyes with no iRORA and no SDD and no iRORA but with SDD experienced a decrease in VA only at months 18 and 24 from baseline.\u003c/p\u003e \u003cp\u003eStudy eyes irrespective of fellow eyes having or not having exudative AMD showed a VA decline by month 24 in LMEM analysis: -1.96 ETDRS letters (95% CI -2.85,-1.07) in eyes with exudative AMD (P\u0026thinsp;\u0026lt;\u0026thinsp;.001) and \u0026minus;\u0026thinsp;2.66 (95% CI -4.43,-0.89) in eyes without exudative AMD (P\u0026thinsp;=\u0026thinsp;.003). However, eyes with GA in the fellow eye maintained better VA across all time points in the study eye, versus study eyes without GA in the fellow eye that showed decline in VA by month 24 (-2.24, SE 0.43, P\u0026thinsp;\u0026lt;\u0026thinsp;.001) and those with GA showing no change.\u003c/p\u003e\n\u003ch3\u003eVA based on better and worse seeing study eye\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e demonstrates the mean baseline VA and change in VA based on better or worse seeing eyes. By 2 years, in eyes with bilateral iAMD, the worse seeing eye changed by -2.8 ETDRS letters (SD 5.1) compared to -1.2 ETDRS letters (SD 7.1) in the better seeing eye (P\u0026thinsp;=\u0026thinsp;0.003). At month 24, study eye VA was 76.8 (SD 10.4) in eyes with exudative AMD in the fellow eye compared to 80.2 (SD 7.9 in study eyes with GA in the fellow eye (P\u0026thinsp;=\u0026thinsp;.002). Study eyes with exudative AMD in the fellow eye changed by -2.1 ETDRS letters (SD 9.6) compared to -0.7 ETDRS letters (SD 8.8) in study eyes with GA in the non-study eye (P\u0026thinsp;=\u0026thinsp;.23).\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e Associations for VA over time by baseline iAMD diagnosis, participant demographic variables and fellow eye status\u003c/span\u003e\u003c/p\u003e \u003cp\u003eIncreased age, lower baseline VA/BCVA and the absence of GA in the fellow eye were associated with reduced VA from baseline across all time points (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and S3). Study eyes with iRORA and SDD also had reduced VA across all time points relative to eyes with no iRORA and no SDD in unadjusted analysis only. Eyes with or without exudative AMD in the fellow-eye had no statistically significant difference in VA in the study eye across all time points.\u003c/p\u003e \u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e Adjusted mean difference in VA over 2 years by study eye diagnosis, participant demographics and fellow eye status\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eM12\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eM18\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eM24\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDifference (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDifference (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDifference (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eDifference (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDifference (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePer 1 year increase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.31(-0.38,-0.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.31(-0.39,-0.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.33(-0.4,-0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.34(-0.42,-0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-0.34(-0.42,-0.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;75\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e75\u0026ndash;84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.78(-3.94,-1.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2.99(-4.18,-1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.21(-4.41,-2.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-3.89(-5.26,-2.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-4.01(-5.46,-2.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e85+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-6.5(-8.27,-4.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-6.81(-8.63,-4.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-7.03(-8.88,-5.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-5.92(-8,-3.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-5.82(-8.05,-3.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.38(-1.51,0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.518\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.51(-1.69,0.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.14(-1.33,1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.811\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.04(-1.39,1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-0.31(-1.75,1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.667\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline VA, ETDRS letters*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-6.52(-7.51,-5.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-7.08(-8.1,-6.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-6.66(-7.85,-5.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-7.34(-8.59,-6.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-17.12(-18.8,-15.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-13.02(-14.74,-11.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-13.27(-15.23,-11.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-12.81(-14.91,-10.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline BCVA, ETDRS letters*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-6.22(-7.32,-5.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-7.26(-8.44,-6.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-6.92(-8.35,-5.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-7.53(-9.08,-5.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-14.34(-16.44,-12.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-11.62(-13.87,-9.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-11.32(-13.99,-8.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-10.43(-13.39,-7.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eiAMD diagnosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo atrophy \u0026amp; no SDD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eRef\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo atrophy \u0026amp; SDD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.3(-1.54,0.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.635\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.31(-0.97,1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.632\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.49(-0.81,1.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.464\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.87(-0.61,2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-0.2(-1.77,1.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.801\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eiRORA \u0026amp; no SDD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.12(-1.76,1.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.889\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.02(-1.73,1.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.986\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.76(-1.01,2.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.56(-0.42,3.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.84(-1.25,2.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eiRORA \u0026amp; SDD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.76(-2.34,0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.21(-2.88,0.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.153\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-1.44(-3.11,0.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-1.37(-3.25,0.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-1.34(-3.32,0.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.187\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExudative AMD in fellow eye**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.39(-2.05,1.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.642\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00(-1.77,1.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.997\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.48(-2.23,1.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.593\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-0.51(-2.58,1.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.631\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.04(-2.08,2.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.971\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGA in fellow eye**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.9(-0.18,3.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.19(0,4.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.050\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.85(0.66,5.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.21(0.61,5.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e3.35(0.69,6.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy; ETDRS-Early treatment Diabetic Retinopathy Study; BCVA-best corrected visual acuity; VA-visual acuity.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003e*For variables baseline VA and BCVA, the outcome was not defined to include baseline time. Eyes with missing baseline VA were not included, a total of N\u0026thinsp;=\u0026thinsp;950 eyes from 782 participants were included for modelling.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003e**For exudative and GA variables in the fellow eye, clustering by eye was not considered, as only one eye per participant was included, and clustering was based solely on time\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eChange in VA: 5- and 10-letter loss across 2 years from baseline\u003c/h2\u003e \u003cp\u003eA total of 188/842 (22.8%) eyes had a 5 or more-letter loss at 1 year and 68/842 (8.1%) eyes lost 10 or more letters (Table \u003cspan refid=\"MOESM4\" class=\"InternalRef\"\u003eS4\u003c/span\u003e). At 2 years, a total of 303/935 (32.4%) had a 5 or more-letter loss and 124/935 (13.3%) lost 10 or more letters (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Higher baseline VA had increased odds of 5-letter VA loss by 1 year (adjusted OR 1.03 per 1 letter increase, 95% CI 1.01\u0026ndash;1.06, P\u0026thinsp;=\u0026thinsp;0.004). Similarly, eyes with increased BCVA were at increased odds of 5 letter loss in VA by 1 year (adjusted OR 1.03, 95% CI 1.00-1.06, P\u0026thinsp;=\u0026thinsp;0.024). By 2 years, eyes with iRORA and no SDD had reduced odds of 5-letter (adjusted OR 0.57, 95% CI 0.35\u0026ndash;0.93, P\u0026thinsp;=\u0026thinsp;0.024) and 10-letter VA loss (adjusted OR 0.42, 95% CI 0.18\u0026ndash;0.96, P\u0026thinsp;=\u0026thinsp;0.039) compared to eyes with no iRORA and no SDD (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). At baseline, presence of GA in the fellow eye was associated with reduced odds of 5-letter VA loss by 1 year (OR 0.29, 95% CI 0.11\u0026ndash;0.65, P\u0026thinsp;=\u0026thinsp;.005) and at 2 years (adjusted OR 0.38, 95% CI 0.19\u0026ndash;0.71, P\u0026thinsp;=\u0026thinsp;0.004) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u0026amp; S5). In addition, eyes with GA in the fellow eye had reduced odds of 10-letter loss in VA by 2 years (adjusted OR 0.26, 95% CI 0.06\u0026ndash;0.72, P\u0026thinsp;=\u0026thinsp;0.026). Unadjusted logistic regression analysis is presented in table \u003cspan refid=\"MOESM6\" class=\"InternalRef\"\u003eS6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProportion of 5 letter and 10 letters losers at 2 years using age and gender adjusted logistic regression models via generalized estimating equations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5 letters \u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;632\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;=5 letters \u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;303\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10 letters\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;811\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;=10 letters \u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;124\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge_cat\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;75\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e290 (45.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e366 (45.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e75\u0026ndash;84\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270 (42.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147 (48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.31 (0.96\u0026ndash;1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e349 (43.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68 (54.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.57 (1.03\u0026ndash;2.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.037\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e85+\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (11.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.17 (0.73\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e96 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10 (8.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.86 (0.41\u0026ndash;1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.01(8.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.96(7.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.02 (1.00\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e75.18(8.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e76.27(6.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.02 (1.00\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e422 (66.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e194 (64.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e541 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e75 (60.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e210 (33.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09 (0.81\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e270 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49 (39.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.29 (0.87\u0026ndash;1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy eye diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo iRORA \u0026amp; no SDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e201 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108 (35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e264 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e45 (36.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo iRORA \u0026amp; SDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e236 (37.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e126 (41.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.97 (0.70\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e311 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e51 (41.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.97 (0.62\u0026ndash;1.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eiRORA \u0026amp; no SDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57 (0.35\u0026ndash;0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e103 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.42 (0.18\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.039\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eiRORA \u0026amp; SDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (14.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72 (0.46\u0026ndash;1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e133 (16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.99 (0.56\u0026ndash;1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVA, ETDRS letters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e404 (63.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e215 (71.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e543 (67.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e76 (61.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e173 (27.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76 (25.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.75 (0.53\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e206 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43 (34.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.43 (0.93\u0026ndash;2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.38 (0.20\u0026ndash;0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.64 (0.26\u0026ndash;1.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVA, ETDRS letters, V1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81(7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.04 (1.02\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e80(6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.00 (0.98\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBCVA, ETDRS letters, V1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e80 or better\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e263 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e156 (73.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e366 (68.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e53 (60.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e70\u0026ndash;79\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (24.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67 (0.45\u0026ndash;1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e133 (24.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e33 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.65 (0.99\u0026ndash;2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;=69\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22 (0.08\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e35 (6.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.21 (0.03\u0026ndash;1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBCVA, ETDRS letters, V1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81(7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05 (1.02\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e80(6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.00 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExudative in the fellow eye\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e603\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e105 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14 (16.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e313 (78.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e171 (83.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.28 (0.83\u0026ndash;2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e413 (79.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e71 (83.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.25 (0.69\u0026ndash;2.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGA in the fellow eye\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e603\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e341 (85.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e194 (94.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e453 (87.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e82 (96.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.38 (0.19\u0026ndash;0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.26 (0.06\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.026\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eAbbreviations: iAMD-intermediate age related macular degeneration; iRORA- incomplete retinal and retinal pigment epithelial atrophy; SDD-subretinal drusenoid deposits; GA-Geographic atrophy. ** glm logistic regression models fitted as only a single eye was included\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eIn sensitivity analysis with BCVA as the outcome, there was negligible difference in predicted BCVA over time (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). At month 24, 53 (5.4%) eyes had progressed to GA and 79 (8.0%) eyes had exudative AMD. After excluding study eyes that developed exudative AMD or GA during the study, there was negligible difference in predicted VA over time (Figure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Additionally, eyes with missing VA over time were similar in distribution in baseline VA and study eye diagnoses to those with available data (Table \u003cspan refid=\"MOESM7\" class=\"InternalRef\"\u003eS7\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrates that individuals with iAMD show minimal change in VA with an average loss of approximately 2 ETDRS letters over 2 years in the real-world irrespective of whether routinely collected VA or BCVA is used in the analysis. In the repeatability study within the MACUSTAR prospective cohort, the mean deviation of BCVA for each AMD group (early, intermediate and late AMD) was also within 2 ETDRS letters.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e About 90% of individuals in our study presented with VA 70 letters or better and around 65% with at least 80 letters and so most individuals with iAMD have good vision creating a ceiling effect and therefore are more prone to lose rather than gain in VA. Only 13% had a 10 or more-letter loss by 2 years, an accepted criterion used to define a minimum clinically meaningful change in AMD and retinal vascular diseases. These results reinforce the fact that a prevention of 15 letter loss is not an achievable endpoint in iAMD if the control arm has a mean loss of only 2 letters over two years and very few eyes lost 10 or more letters.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThese results also highlight the importance of baseline VA when evaluating and comparing clinical trials in iAMD. Those presenting with less than 70 letters, are also more likely to show an improvement in VA over the 2 years (mean\u0026thinsp;+\u0026thinsp;2.39 ETDRS letters) compared to those presenting with VA of at least 80 letters (mean-1.9 ETDRS letters). It is well-established that lower VA present with greater variability and have a floor effect. Therefore, including patients with iAMD and VA less than 70 letters in clinical trials are more likely to result in surprising results especially if the intervention and control arms are not balanced for visual acuity. In addition, these findings may be interpreted as regression to the mean too.\u003c/p\u003e \u003cp\u003eAnother factor to consider is that increasing age at baseline was linked to lower VA across all time points (6,12, 18 and 24 months), with a decrease of -0.34 letters per year of baseline age at 24 months. Individuals aged 75\u0026ndash;84 and those\u0026thinsp;\u0026ge;\u0026thinsp;85 years had lower VA outcome at all time points compared to \u0026lt;\u0026thinsp;69 age group irrespective of whether VA or BCVA was used for the analysis. Multiple age-related ocular changes including increasing thickness of the Bruch\u0026rsquo;s membrane, lipid accumulation, drusen volume and decreasing density of choriocapillaris may explain this observation.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The changes may also be confounded by non-AMD related VA decline with time.\u003c/p\u003e \u003cp\u003eInterestingly, based on our classification of iAMD phenotypes, all groups showed a mean decline in VA over two years with no difference in mean change between them. After excluding study eyes that developed exudative AMD or GA during the study, there was negligible difference in predicted VA over time. Although eyes with SDD presented with lower VA and remained so at two years, the mean change did not reach statistical significance, in contrast to previous reports from smaller studies.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e On the contrary, by 2 years, eyes with iRORA with no SDD had reduced odds of 5-letter (adjusted OR 0.57, 95% CI 0.35\u0026ndash;0.93, P\u0026thinsp;=\u0026thinsp;0.024) and 10-letter VA loss (adjusted OR 0.42, 95% CI 0.18\u0026ndash;0.96, P\u0026thinsp;=\u0026thinsp;0.039) compared to eyes with no iRORA and no SDD. These findings highlight that although iRORA is a risk factor for transition to cRORA, this structural precursor of atrophy is not associated with VA decline. Moreover, these findings may also be because iRORA may be reversible.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur results also show that study eyes with GA in the fellow eye had reduced odds of both 5 and 10-letter loss in VA by 2 years. These observations demonstrate the slow course of the transition from iAMD to atrophy without substantial VA loss. In fact, the presence of GA in the fellow eye was associated with an improved VA outcome in the study eye across all time points, with a mean improvement of 3.35 letters at month 24 relative to study eyes without GA in the fellow eye. This finding raises the question whether participants with fellow eye GA attempts to read better at each visit than those without GA in the fellow eye. These within 1-line changes in VA in the natural course of iAMD has been confirmed in other studies and should also be considered when interpreting clinical trials in iAMD. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough this is a large cohort with iAMD, the study has some limitations. The classification of eyes as presence or absence of SDD may be imperfect as the quantity or area of SDD may need to be incorporated for finer phenotyping.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Furthermore, the definition of iAMD assumes soft drusen are distributed in the macula and other risk characteristics of drusen such as hyporeflective drusen, cuticular drusen and drusenoid pigment epithelial detachment may also influence disease progression.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e A more detailed grading of iAMD may elicit functional changes not revealed in this study. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDespite these limitations, the findings of this large cohort study provide insights for further research on VA change in iAMD especially for designing future clinical trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCorresponding Author\u003c/strong\u003e: Sobha Sivaprasad, National Institute of Health Research Moorfields Biomedical Research Centre and Clinical Research Facility, Moorfields Eye Hospital, 162, City Road, London, EC1V 2PD, UK. Email: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u003c/strong\u003e The investigator-initiated study was funded by Boehringer Ingelheim International GmbH.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures\u003c/strong\u003e: Dr. Sivaprasad reported receiving financial support from AbbVie, Adverum, Amgen, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Pharmaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics and Sanofi. Sobha Sivaprasad is the Editor-in-Chief of EYE.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e The data that support the findings of this study are all reported in this paper. Further details are available from the corresponding author and/or in the EVICR.net Eye Platform upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng Y, Qiao L, Du M, Qu C, Wan L, Li J, Huang L: Age-related macular degeneration: epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy. Genes Dis. 2022, 9:62\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR; Beckman Initiative for Macular Research Classification Committee. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120(4):844\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCsaky KG, Richman EA, Ferris FL 3rd: Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium. Invest Ophthalmol Vis Sci. 2008, 49:479\u0026thinsp;\u0026ndash;\u0026thinsp;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeck RW, Maguire MG, Bressler NM, Glassman AR, Lindblad AS, Ferris FL. Visual acuity as an outcome measure in clinical trials of retinal diseases. Ophthalmology. 2007;114(10):1804\u0026ndash;1809.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmetterer L, Scholl H, Garh\u0026ouml;fer G, Janeschitz-Kriegl L, Corvi F, Sadda SR, Medeiros FA: Endpoints for clinical trials in ophthalmology. Prog Retin Eye Res. 2023, 97:101160.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaldstein SM, Vogl WD, Bogunovic H, Sadeghipour A, Riedl S, Schmidt-Erfurth U. Characterization of Drusen and Hyperreflective Foci as Biomarkers for Disease Progression in Age-Related Macular Degeneration Using Artificial Intelligence in Optical Coherence Tomography. JAMA Ophthalmol. 2020;138(7):740\u0026ndash;747.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLad EM, Finger RP, Guymer R. Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration. Ophthalmol Ther. 2023;12(6):2917\u0026ndash;2941.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSadda SR, Guymer R, Holz FG, Schmitz-Valckenberg S, Curcio CA, Bird AC, Blodi BA, Bottoni F, Chakravarthy U, Chew EY, Csaky K, Danis RP, Fleckenstein M, Freund KB, Grunwald J, Hoyng CB, Jaffe GJ, Liakopoulos S, Mon\u0026eacute;s JM, Pauleikhoff D, Rosenfeld PJ, Sarraf D, Spaide RF, Tadayoni R, Tufail A, Wolf S, Staurenghi G. Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3. Ophthalmology. 2018;125(4):537\u0026ndash;548. doi: 10.1016/j.ophtha.2017.09.028. Epub 2017 Nov 2. Erratum in: Ophthalmology. 2019;126(1):177.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Z, Fletcher EL, Kumar H, Greferath U, Guymer RH. Reticular pseudodrusen: A critical phenotype in age-related macular degeneration. Prog Retin Eye Res. 2022;88:101017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDunbar HMP, Behning C, Abdirahman A, Higgins BE, Binns AM, Terheyden JH, Zakaria N, Poor S, Finger RP, Leal S, Holz FG, Schmid M, Crabb DP, Rubin GS, Luhmann UFO; MACUSTAR Consortium. Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report. JAMA Ophthalmol. 2022;140(8):780\u0026ndash;789.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePauleikhoff D, Harper CA, Marshall J, Bird AC.. Aging changes in Bruch's membrane: a histochemical and morphological study. Ophthalmology. 1990; 97: 171\u0026ndash;178.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCurcio CA, Kar D, Owsley C, Sloan KR, Ach T.. Age-related macular degeneration, a mathematically tractable disease. Invest Ophthalmol Vis Sci. 2024; 65: 4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrewal MK, Chandra S, Gurudas S, Rasheed R, Sen P, Menon D, Bird A, Jeffery G, Sivaprasad S. Functional clinical endpoints and their correlations in eyes with AMD with and without subretinal drusenoid deposits-a pilot study. Eye (Lond). 2022;36(2):398\u0026ndash;406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSantamar\u0026iacute;a J, Pagani F, Mon\u0026eacute;s J. Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy? Eur J Ophthalmol. 2024 Oct 15:11206721241290263.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaiser PK. Prospective evaluation of visual acuity assessment: a comparison of snellen versus ETDRS charts in clinical practice (An AOS Thesis). Trans Am Ophthalmol Soc. 2009;107:311\u0026thinsp;\u0026ndash;\u0026thinsp;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeng T, Schwartz J, Nimke D, Gallivan M, Fevrier H, Rozario N, Schultz NM. Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. Ophthalmol Ther. 2023;12(1):325\u0026ndash;340.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLad EM, Fang V, Tessier M, Rautanen A, Gayan J, Stinnett SS, Luhmann UFO. Longitudinal Evaluation of Visual Function Impairments in Early and Intermediate Age-Related Macular Degeneration Participants. Ophthalmol Sci. 2022;2(3):100173.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchneck ME, Lott LA, Haegerstrom-Portnoy G, Hewlett S, Gauer BM, Zaidi A. Visual Function in Eyes with Intermediate AMD with and without Retinal Pigment Abnormalities. Optom Vis Sci. 2021;98(1):64\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavis MD, Gangnon RE, Lee LY, Hubbard LD, Klein BEK, Klein R, Ferris FL, Bressler SB, Milton RC, Group AREDS The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005;123(11):1484\u0026ndash;1498.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6247988/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6247988/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground/Objectives:\u003c/h2\u003e \u003cp\u003eThe aim of this study was to evaluate the change in visual acuity (VA) in participants with intermediate age-related macular degeneration (iAMD) over two years when categorized by the presence or absence of incomplete retinal and retinal pigment atrophy (iRORA) and subretinal drusenoid deposits (SDD).\u003c/p\u003e\u003ch2\u003eSubjects/Methods:\u003c/h2\u003e \u003cp\u003eIn this multicentre cohort study, participants with iAMD were classified as: i) iAMD with no iRORA or SDD; ii) iAMD with SDD with no iRORA; iii) iAMD with iRORA with no SDD and iv) iAMD with iRORA and SDD. The change in VA over two years in the whole cohort and in each sub-category was analysed using a linear mixed effect model employing an unstructured covariance structure. Associations with age, sex and baseline VA were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e983 eyes from 805 participants were analysed. The mean baseline VA changed from 79.8 (SD 8.1) to 78 (SD 10.1) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at two years. All sub-categories showed a small decline in VA. The group with both iRORA and SDD experienced a statistically significant decline in VA from baseline across all time points (6,12, 18 and 24 months) and by month 24 a change of -2.72 ETDRS letters (95% CI -4.16, -1.28), P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 was observed. Increasing age and lower baseline visual acuity were associated with lower VA over two years.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEyes with iAMD experience a small mean decline of approximately 2 letters over two years. Overall, these changes may not represent a clinically meaningful difference.\u003c/p\u003e","manuscriptTitle":"Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 12:12:59","doi":"10.21203/rs.3.rs-6247988/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-06-10T09:55:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-05T00:10:29+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-16T01:23:53+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-10T22:24:26+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-04-21T19:56:31+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-04-01T12:59:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-27T08:52:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-19T14:45:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2025-03-17T23:20:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7c41e2c6-78cc-4752-8737-d91dc2b048e9","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":46521474,"name":"Health sciences/Biomarkers"},{"id":46521475,"name":"Health sciences/Biomarkers/Predictive markers"}],"tags":[],"updatedAt":"2025-10-18T07:08:57+00:00","versionOfRecord":{"articleIdentity":"rs-6247988","link":"https://doi.org/10.1038/s41433-025-04062-z","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2025-10-17 04:00:00","publishedOnDateReadable":"October 17th, 2025"},"versionCreatedAt":"2025-04-30 12:12:59","video":"","vorDoi":"10.1038/s41433-025-04062-z","vorDoiUrl":"https://doi.org/10.1038/s41433-025-04062-z","workflowStages":[]},"version":"v1","identity":"rs-6247988","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6247988","identity":"rs-6247988","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}